Project Summary Over 86 million people in the U.S. have cardiovascular disease and 100 million have diabetes or prediabetes. This already-high prevalence continues to increase, posing major threats to societal health and well-being. Diabetes and cardiovascular disease are thought to arise from a common soil, namely insulin resistance, dyslipidemia, pro-inflammatory/pro-coagulation states and abdominal obesity, conditions which underlie the metabolic syndrome (MetS). While MetS is a viable concept for identifying individuals with increased disease risk, the clinical criteria and cutoffs do not detect the earliest abnormalities. Yet, the successful prevention of type 2 diabetes and atherosclerotic vascular disease hinges on early detection and intervention. In a recent study of 72 generally healthy non-diabetic adults, we discovered a powerful and practical biomarker that detects a constellation of early metabolic abnormalities with just one measurement. This biomarker is measured as a decrease in plasma or serum water T2 using compact nuclear magnetic resonance relaxometry. The overall objective of the proposed study is to validate water T2 as a biomarker for cardiometabolic health using a large, diverse cohort. The overarching hypothesis is that water T2 is exquisitely sensitive to the early metabolic abnormalities indicative of diabetes and cardiovascular risk. The specific aims are: (1) Quantify the association of plasma and serum water T2 with metabolic syndrome and its individual components in a large cohort; (2) Measure the responsiveness of water T2 to lifestyle interventions designed to reduce blood pressure and improve cardiometabolic health; and (3) Define the sensitivity, specificity and cutoff values of water T2 for detecting early abnormalities, including insulin resistance, subclinical inflammation and dyslipidemia. This project will analyze biobanked plasma and serum samples from the PREMIER study, an already-completed randomized controlled trial funded by the NHLBI. To the PREMIER database, we will add plasma and serum water T2 values for 707 subjects, as well as other proteomic measures related to cardiometabolic health and disease risk. The proposed project represents an exceptional opportunity to validate water T2 as a global biomarker for cardiometabolic health, while expanding the PREMIER database and increasing the value of the parent study.